About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids), I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 17 terrific physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow to better the outcomes for children with inflammatory bowel disease – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have helped enroll patients in industry-sponsored research studies.

Aerodigestive Complexity Score

Posted on November 13, 2023 by gutsandgrowth

HM Horita et al. J Pediatr 2023; 261: 113549. Open Access! Development of a Medical Complexity Score for Pediatric Aerodigestive Patients

Methods: The authors in this study developed a 7-point medical complexity score . One point was assigned for each comorbid diagnosis in the following categories: airway anomaly, neurologic, cardiac, respiratory, gastrointestinal, genetic diagnoses, and prematurity. A retrospective chart review was conducted of patients (n=234) seen in the aerodigestive clinic who had ≥2 visits between 2017 and 2021.

Improvements were followed in the Functional Oral Intake Scale (FOIS)–assigned by aerodigestive feeding therapists.⁶ The FOIS scale is as follows:

•1 = Nothing by mouth
•2 = Tube-dependent with minimal attempts of food or liquids (<10%)
•3 = Tube-dependent with consistent oral intake of food or liquids
•4 = Total oral diet of a single consistency
•5 = Total oral diet with multiple consistencies, but requiring special preparations or compensations
•6 = Total oral diet with multiple consistencies without special preparation, but with specific food limitations
•7 = Total oral diet with no restriction, or <12 months of age on age-appropriate diet

Key findings:

At presentation, 69.5% were not at unrestricted age-appropriate diet; 22.7% of the cohort (n = 53) were completely tube dependent
There were 165 patients who were not at unrestricted total age-appropriate oral diet at presentation, and the majority (54% [n = 90]) showed improvement in their FOIS scores after aerodigestive team intervention.
“For each 1-unit increase in complexity score, there was a 33% decrease in the odds of improvement in FOIS scores (OR, 0.66; 95% CI, 0.51-0.84; P = .001);” however, only neurological comorbidity (OR, 0.26; 95% CI, 0.13-0.53; P < .001) and airway anomaly (OR, 0.35; 95% CI, 0.15-0.79; P = .01) were significantly associated with decreased likelihood to progress in feeding based on FOIS scores
Of the 125 patients who were tube fed at initial presentation, 20% (n = 25) were able to achieve full oral feeding after intervention

My take: While the complexity score did correlate with likelihood of progressing with oral feedings, it appears that this score is unnecessary as likelihood of progressing is mainly related to two factors: neurological comorbidities and airway anomalies.

Related blog posts:

Current Approach for FPIES

Posted on November 10, 2023 by gutsandgrowth

Our excellent nutritionist, Bailey Koch, recently gave our group a terrific update on FPIES. Bailey is part of the medical advisory board for THE FPIES Foundation, as is Dr. Benjamin Gold from our group. Here are many of the slides from her lecture.

Link: FPIES foundation action plan sheet:

From International guidelines:
Nowak-Węgrzyn A, Chehade M, Groetch ME, et al. **Open Access**: International consensus guidelines for the diagnosis and management of food protein-induced enterocolitis syndrome: Executive summary-Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2017;139:1111-26.

Atlantis Study: Possibly Best Evidence That Tricyclics May Help Irritable Bowel

Posted on November 9, 2023 by gutsandgrowth

Thanks to Ben Gold for this reference.

AC Ford et al. The Lancet 2023; DOI:https://doi.org/10.1016/S0140-6736(23)01523-4. Open Access! Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial

In this randomized, double-blind, placebo-controlled study of 463 adults (median age 48 yrs), the authors compared low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months, with dose titration over 3 weeks (up to 30 mg once daily). The use of the Rome IV criteria resulted in the selection of a group of patients with higher symptom severity,⁵⁰ borne out by the mean IBS-SSS scores at baseline, which were in the moderate to severe range. The median duration of IBS among participants was 10 years.

Key findings:

Intention-to-treat analysis of the primary outcome showed a significant difference in favour of low-dose amitriptyline in IBS-SSS score between groups at 6 months (–27·0, 95% CI –46·9 to –7·10; p=0·0079)
46 (20%) participants discontinued low-dose amitriptyline (30 [13%] due to adverse events), and 59 (26%) discontinued placebo (20 [9%] due to adverse events) before 6 months.

In their discussion, the authors note that “this is the largest trial of a tricyclic antidepressant in IBS ever undertaken and the first based entirely in a primary care setting…low-dose amitriptyline met the primary outcome, with a mean decrease in IBS-SSS of almost 100 points at both months 3 and 6 compared with baseline, and also met the key secondary outcome for effectiveness, as well as other IBS symptom measures.”

“There was no effect of low-dose amitriptyline on somatoform symptom-reporting scores, or anxiety or depression scores, during 6 month follow-up, nor was there any impact on work and social activities.:

**Key secondary outcome of SGA of relief of IBS symptoms at 6 months**. SGA=subjective global assessment.

My take (borrowed from authors): Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple outcomes, and was safe and well tolerated.

COMBO-IBD Study -Combination Immunomodulator Use and Thresholds

Posted on November 8, 2023 by gutsandgrowth

AJ Yarur et al. Clin Gastroenterol Hepatol 2023; 21: 2908-2917. Open Access! Combination Therapy With Immunomodulators Improves the Pharmacokinetics of Infliximab But Not Vedolizumab or Ustekinumab

In this prospective cohort with 369 patients, treatment included the following 113 infliximab, 133 vedolizumab, and 123 ustekinumab. All patients received standard dosing (eg. 5 mg/kg/dose every 8 weeks with infliximab). Per Table 1, dose of thiopurine was 100 mg (range 50-150, “using a 2:1 ratio of azathioprrine and mercaptopurine”); most patients received methotrexate at a dose of 12.5 mg. Key findings:

Infliximab levels were much improved in patients receiving combination therapy with either a thiopurine or methotrexate. In those patients receiving a thiopurine, a threshold of 6-TGN ≥146 was considered optimal.
Patients receiving combination therapy with methotrexate or a thiopurine and a 6-TGN concentration ≥146 pmol per 8 × 10⁸ RBCs, and those with baseline infliximab level ≥12.3 μg/mL had a lower rate of secondary nonresponse when compared with those on monotherapy, thiopurine with 6-TGN <146 pmol per 8 × 10⁸ RBCs, and baseline infliximab level <12.3 μg/mL (88.2 vs 11.8% [P = .04], 71.2 vs 45.5% [P = .04])

Ustekinumab and vedolizumab levels were NOT increased in patients receiving an immunomodulator

My take: This study reinforces the idea that there are pharmacokinetic benefits of combination therapy with infliximab (and extrapolated to other anti-TNF agents); there is a lack of benefit for most patients receiving ustekinumab and vedolizumab. Even with ustekinumab and vedolizumab, it is possible that patients with more severe disease may still benefit independent of pharmacokinetic effects on biologic agent.

Higher doses of infliximab monotherapy with therapeutic drug monitoring may achieve similar results as combination therapy. However, patients switching from one anti-TNF to another due to immunogenicity/antidrug antibodies are particularly likely to benefit from combination therapy. In addition, a recent ImproveCareNow study showed better outcomes for pediatric patients who received methotrexate with adalimumab (see below).

Related blog posts:

Why It is Still Not a Good Idea to Test Healthy Children for Enteric Pathogens & Infant Mortality Rates Rising in Georgia (& much of U.S.)

Posted on November 7, 2023 by gutsandgrowth

BR Lee et al. J Pediatr 2023; 261: 113551. A Comparison of Pathogen Detection and Risk Factors among Symptomatic Children with Gastroenteritis Compared with Asymptomatic Children in the Post-rotavirus Vaccine Era

Patients (<11 yrs old) with acute gastroenteritis (AGE, n=2503) and healthy controls (HC, n=537) old enrolled in the New Vaccine Surveillance Network study between December 2011 to June 2016. Key findings:

One or more organisms was detected in 1159 of 2503 children (46.3%) with AGE compared with 99 of 537 HC (17.3%).
Norovirus was detected most frequently among AGE (n = 568 [22.7%]). The other frequent pathogens detected were rotavirus 7.8% (despite ~75% vaccinated population), adenovirus 4.8%, C difficile 5.3%, Salmonella 6.4%, and Shigella 4.5%. 63.5% of all pathogens detected were viruses.
C difficile was detected more frequently in the HC population (7% vs 5.3%). E coli infections, likewise, were very commonly observed in the HC population (2.1% vs 1.1%). The false positive rates for C difficile pathogenicity would have been higher if the authors had not restricted their analysis to >12 months for C diff. The rates of Norovirus and Rotavirus in the HC group was 6.8% and 2.6% respectively.
Codetection of multiple pathogens was common. For example, with norovirus, 20.8% had a copathogen detected. Salmonella and C difficile had the highest codection rates of 53.5% and 54.5% respectively.

This study shows substantial improvement in rotavirus infections with a drop from 26% in detection prior to vaccine era to 6% afterwards.

My take: These muliplex molecular assays are quite useful and have improved our ability to determine underlying infections. This is particularly useful in children with underlying diseases (eg. IBD, malignancy). However, this report serves as a cautionary note that many pathogens, including C diff and E coli, are frequently identified with PCR assays in healthy children

Related blog posts:

In 2022, 892 infants died in Georgia, an increase of 116 from prior year. About 7 infants dying for every 1000 births. AJC 11/1/23: CDC: Georgia’s infant mortality increase is among the worst in U.S.

Increasing Prevalence of Steatotic Liver Disease in Adolescents

Posted on November 6, 2023 by gutsandgrowth

P Hartmann et al. Hepatology 2023; 78: 1168-1181. Open Access! Global and national prevalence of nonalcoholic fatty liver disease in adolescents: An analysis of the global burden of disease study 2019

The authors analyzed data from the Global Burden of Disease Study 2019 to compare global, continental, and national prevalence rates of adolescent (15-19 yrs of age) NAFLD.

Key finding:

The global NAFLD prevalence in adolescents increased from 3.73% in 1990 to 4.71% in 2019 (a relative increase of 26.27%). NAFLD is now termed metabolic dysfunction-associated steatotic liver disease (MASLD).
High body mass index and not type 2 diabetes mellitus correlated with NAFLD prevalence in adolescents globally.

In the associated editorial (S Xanthakos, Hepatology 78(4):p 1017-1019, October 2023, Rising tide of NAFLD in youth: A warning bell and call to action), some of the key points:

“The Global Burden of Disease (GBD) Study is the most comprehensive and long-standing effort to systematically and scientifically collate data on hundreds of diseases and injuries across the globe, including related clinical outcomes. Beginning in 1990, the GBD Study initially collected data on 106 conditions and 10 risk factors, across 5 age groups.¹ Over time, the GBD Study has expanded through serial iterations to involve >9000 international researchers collecting data on 369 diseases and injuries across 204 countries and territories in the most recent 2019 report.¹“
” From the GBD Study, we learned that NAFLD is the most rapidly rising cause of chronic liver disease in adolescents and adults,² and the fastest-growing contributor to cirrhosis, liver cancer, and liver-related deaths globally.”
“The global prevalence of NAFLD in adolescents shows no sign of abating, rather has continued to increase steadily from 3.7% in 1990 to 4.7% in 2019.”
“As with all epidemiological research, the GBD study faces the primary limitation of relying on data sources that employ varying and less accurate measures of NAFLD prevalence (alanine aminotransferase and/or ultrasound primarily). However, the rigorous methodological approach employed by the GBD including frequent assessment of face validity, and the tremendous input of data sources (>80,000 in 2019) nonetheless results in the most comprehensive global data set available.”

My take (borrowed from editorial): Without intervention, “the increase in adolescent NAFLD certainly portends a future increase in NAFLD-related cirrhosis and liver-related deaths in young adults in the coming decades, and a likely escalation in cardiovascular and diabetes-related morbidity.

Related blog posts:

Flu Shots & Other Vaccines Linked to Lower Rates of Dementia

Posted on November 5, 2023 by gutsandgrowth

10/26/23 Washington Post: Flu shots may protect against the risk of Alzheimer’s, related dementias

An excerpt:

A number of studies have found that people receiving vaccinations for flu and several other infectious diseases appear less likely than the unvaccinated to develop dementia, although scientists aren’t sure why…

In the flu study, the researchers took participants from a national patient database, two groups of 935,887 each, one group vaccinated, the other not. To avoid the potential influence of various factors that could affect the results, the scientists ensured that each group shared many of the same characteristics… found that an annual flu vaccination for three consecutive years reduced the dementia risk 20 percent over the next four to eight years, while six shots doubled it to a 40-percent reduction…

“All this requires further studies, but vaccination, along with good diet, exercise, intellectual and emotional stimulation are key factors for healthy aging,” Hotez said.

The article notes reductions in dementia with Shingles vaccine, Tdap or Td, and pneumococcal vaccines.

These cliffs of the calanques (near Cassis, France) are about 260 meters in elevation

Upadacitinib Works Quickly and with High Response

Posted on November 3, 2023 by gutsandgrowth

D Ahuja et al. Am J Gastroenterol 2023; Open Access! Comparative Speed of Early Symptomatic Remission With Advanced Therapies for Moderate-to-Severe Ulcerative Colitis: A Systematic Review and Network Meta-Analysis Thanks to Ben Gold for this article.

Key findings:

On network meta-analysis of 14 RCTs, upadacitinib was more effective than all agents in achieving symptomatic remission at weeks 2 (range of RR, 2.85–6.27), 4 (range of RR, 1.78–2.37), and 6 (range of RR, 1.84–2.79).

This study has a number of limitations including the following:

Potential differences in patient-level characteristics between these trials
Symptoms may not always correlate with endoscopic findings
Data from some medications (eg. tofacitinib) were incomplete and not included

My take: This study indicates an impressive early symptomatic response to upadacitinib compared to other agents for ulcerative colitis.

Related blog posts:

Three-fer on Steatotic Liver Disease

Posted on November 2, 2023 by gutsandgrowth

JJ Wattacheril, MF Abdelmalek et al. Gastroenterol 2023; 165: 1080-1088. Open Access! AGA Clinical Practice Update on the Role of Noninvasive Biomarkers in the Evaluation and Management of Nonalcoholic Fatty Liver Disease: Expert Review

This article offers best practice advice -here are two of them:

#2: A Fibrosis 4 Index score <1.3 is associated with strong negative predictive value for advanced hepatic fibrosis and may be useful for exclusion of advanced hepatic fibrosis in patients with NAFLD.

#8 Patients with NAFLD and NITs (noninvasive tests) results suggestive of advanced fibrosis (F3) or cirrhosis (F4) should be considered for surveillance of liver complications (eg, hepatocellular carcinoma screening and variceal screening per Baveno criteria). Patients with NAFLD and NITs suggestive of advanced hepatic fibrosis (F3) or (F4), should be monitored with serial liver stiffness measurement; vibration controlled transient elastography; or magnetic resonance elastography, given its correlation with clinically significant portal hypertension and clinical decompensation.

2. AJ Sanyal et al. Clin Gastroenterol Hepatol 2023; 21: 2889-2900. Validation of a Clinical Risk-based Classification System in a Large Nonalcoholic Fatty Liver Disease Real-world Cohort

In this study from U.S., patients (n=2523) were divided into three categories based on FIB-4 scores: (A) Fibrosis-4 (FIB-4) <1.3 and/or liver-stiffness measurement (LSM) measured by Fibroscan <8 kp, (B) FIB-4 1.31‒2.6 and/or LSM 8.1-12.5 kp, and (C) FIB-4 >2.6 and/or LSM >12.5 kp. However, those in class A with aspartate transaminase:alanine transaminase ratio >1 or platelets <150,000/mm³, or class B with aspartate transaminase:alanine transaminase ratio >1 or platelets <150,000/mm³ were upstaged by one class. The data were reviewed retrospectively from a prospective longitudinal cohort (TARGET-NASH)

Key findings: All adverse outcomes including liver and cardiovascular (see below) were correlated with FIB-4 staging.

S Man et al. Gastroenterol 2023; 165: 1025-1040. Open Access! Prevalence of Liver Steatosis and Fibrosis in the General Population and Various High-Risk Populations: A Nationwide Study With 5.7 Million Adults in China

Key findings: The prevalence of steatosis, severe steatosis, advanced fibrosis, and cirrhosis was 44.39%, 10.57%, 2.85%, and 0.87%, respectively in Chinese adults

Limitation: This data was derived from a health checkup cohort which could give different results than a random population sampling. Patients at health checkups may be more health conscious and/or be aware of underlying health concerns.

**Prevalence of different grades of liver fibrosis in different age groups.**

My take: Steatotic liver disease is a huge worldwide problem. The growing prevalence is going to result in extensive health issues.

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This year’s pumpkin 910/31/23):

It does not look like I will become a professional pumpkin artist anytime soon!

What’s Going on With Refractory Heartburn?

Posted on November 1, 2023 by gutsandgrowth

L Guadagnoli, A Geeraerts et al. Gastroenterol 2023; 165: 848-860. Open Access! Psychological Processes, Not Physiological Parameters, Are Most Important Contributors to Symptom Severity in Patients With Refractory Heartburn/Regurgitation Symptoms

Methods: Consecutive adult patients (n=393) with refractory heartburn/regurgitation symptoms underwent standard 24-hour pH-impedance monitoring and completed questionnaires assessing past and current gastrointestinal and psychological health. Refractory reflux meant that they continued to have symptoms after completing at least 12 weeks of PPI (twice per day) treatment.

Key findings: Psychological symptoms were significantly associated with reflux symptom severity, and physiological reflux variables (eg, number of reflux episodes) were not.

In the discussion, the authors note that ” prior research demonstrates psychological symptoms, including depression, anxiety, and post-traumatic stress, are associated with reflux symptom severity.^25, 26, 27 Indeed, psychological processes are believed to impact the brain–gut axis, particularly its central components,²⁸ leading to enhanced esophageal symptom perception and reporting.^6,29,30“

My take: Psychological factors (depression, anxiety, post-traumatic stress, and poor sleep) are important factors in refractory reflux and they need to be considered early in the evaluation.

A related article: NY Times Magazine 10/4/23, M Velasques-Manoff. The Mystery of My Burning Esophagus. In this article, the writer describes burning pain associated with his diagnosis of eosinophilic esophagitis. This article has some useful information about eosinophilic esophagitis and about lingering symptoms after responding to treatment.

“My new gastroenterologist had a theory to explain the all-consuming pain under my sternum. Sometimes patients develop a hypersensitivity syndrome, she told me. The original insult — in my case, inflammation of some kind — might be long gone, but the nerves that convey pain can become overactive and begin firing at the slightest provocation…Scientists don’t completely understand how antidepressants help pain syndromes, but certain ones seem to impede pain signals in the nervous system…

Doctors are increasingly aware of these kinds of pain syndromes in many disorders, including GERD. The condition, whose primary symptom is known colloquially as heartburn, is pervasive, afflicting an estimated one in five Americans. Some of these patients continue to feel intense pain even after their stomach acid has been reduced with antacids, a malady most likely caused by a hypersensitivity syndrome similar to mine.”

Related blog posts: